Synthesis of Quinoline and Dihydroquinoline Embelin Derivatives as Cardioprotective Agents. 2023

Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez N° 2, 38206, La Laguna, Tenerife, Spain.

A set of new dihydroquinoline embelin derivatives was obtained from the reaction of the natural benzoquinone embelin (1) with anilines and aromatic aldehydes in the presence of AgOTf. The synthesis of these compounds involves the formation of a Knoevenagel adduct, followed by nucleophilic addition of aniline and subsequent electrocyclic ring closure. The scope of the reaction regarding the aldehydes and anilines was determined. Quinoline derivatives were also obtained from the corresponding dihydroquinolines under oxidation with DDQ. The cardioprotective activity of the synthesized compounds was screened using a doxorubicin-induced cardiotoxicity model in H9c2 cardiomyocytes. Some structure-activity relationships were outlined, and the best activities were achieved with quinoline-embelin derivatives having a 4-nitrophenyl group attached at the pyridine ring. The obtained results indicated that embelin derivatives 4i, 6a, 6d, 6k, and 6m could have potential as cardioprotective agents, as they attenuated a DOX-induced cardiotoxicity effect acting on oxidative stress and apoptosis.

UI MeSH Term Description Entries
D011804 Quinolines
D002316 Cardiotonic Agents Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE). Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000447 Aldehydes Organic compounds containing a carbonyl group in the form -CHO. Aldehyde
D000814 Aniline Compounds Compounds that include the aminobenzene structure. Phenylamine,Phenylamines,Anilines,Compounds, Aniline
D016227 Benzoquinones Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. 1,2-Benzoquinones,1,4-Benzoquinones,Benzodiones,2,5-Cyclohexadiene-1,4-Diones,o-Benzoquinones,p-Benzoquinones
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative
D032383 Myocytes, Cardiac Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC). Cardiomyocytes,Muscle Cells, Cardiac,Muscle Cells, Heart,Cardiac Muscle Cell,Cardiac Muscle Cells,Cardiac Myocyte,Cardiac Myocytes,Cardiomyocyte,Cell, Cardiac Muscle,Cell, Heart Muscle,Cells, Cardiac Muscle,Cells, Heart Muscle,Heart Muscle Cell,Heart Muscle Cells,Muscle Cell, Cardiac,Muscle Cell, Heart,Myocyte, Cardiac

Related Publications

Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
January 1986, Polish journal of pharmacology and pharmacy,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
September 2018, European journal of medicinal chemistry,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
July 1974, Journal of medicinal chemistry,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
July 2021, European journal of medicinal chemistry,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
July 2019, Bioorganic chemistry,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
June 2018, European journal of medicinal chemistry,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
July 2019, Archiv der Pharmazie,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
March 2019, Bioorganic chemistry,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
September 2019, European journal of medicinal chemistry,
Pedro Martín-Acosta, and Irene Cuadrado, and Laura González-Cofrade, and Roberto Pestano, and Sonsoles Hortelano, and Beatriz de Las Heras, and Ana Estévez-Braun
February 2021, Molecules (Basel, Switzerland),
Copied contents to your clipboard!